New huprine derivatives functionalized at position 9 as highly potent acetylcholinesterase inhibitors

A series of 24 huprine derivatives diversely functionalized at position 9 have been synthesized and evaluated for their inhibitory activity against human recombinant acetylcholinesterase (AChE). These derivatives were prepared in one to five steps from huprine 1 bearing an ester function at position 9. Ten analogues ( 1 , 2 , 6 – 9 , 13 – 15 , and 23 ) are active in the low nanomolar range (IC₅₀ <5 nM ), very close to the parent compound huprine X. Compounds 2 , 6 , and 7 show a very good selectivity for AChE, with AChE inhibitory activities 700–1160‐fold higher than those for butyrylcholinesterase (BChE). The inhibitory potency of these compounds decreases with the steric bulk of the substituents at position 9. According to docking simulations, small substituents fit into the acyl‐binding pocket, whereas the larger ones stick out of the active site gorge of AChE. Determination of the kinetic parameters of three of the most potent huprines ( 2 , 6 , and 7 ) showed that most of the difference in K_D is accounted by a decrease in k_on, which is correlated to the increase of the substituent size. A first in vivo evaluation has been performed in mice for the most active compound 2 (IC₅₀=1.1 nM ) and showed a rather weak toxicity (LD₅₀=40 mg kg^?1) and an ability to cross the blood–brain barrier with doses above 15 mg kg^?1.     

Synthesis of ‘ready-to-adsorb’ polymeric nanoshells for magnetic iron oxide nanoparticles via atom transfer radical polymerization

Polymer-magnetite nanoparticle complexes that respond to both magnetic fields and to temperature have been demonstrated. Novel alkyl halide-functional bis(diethylphosphonate) esters were prepared and utilized as initiators for polymerizing N-isopropylacrylamide by controlled atom transfer radical polymerization. The phosphonate esters were removed after polymerization to afford poly(N-isopropylacrylamide) with a bis(phosphonic acid) moiety precisely placed at one terminus. The bis(phosphonic acid) endgroups were adsorbed onto magnetite nanoparticles to yield nanoscale complexes that were stable against any polymer desorption and that were colloidally-stable in physiological media. Thus, the bis(phosphonate) endgroup provides a robust anchoring moiety onto the magnetite. Hydrodynamic sizes of the complexes were predicted with a density distribution model and using the measured sizes of the magnetite cores. Good agreement between the measured and predicted hydrodynamic sizes suggested that the complexes were primarily discrete, non-agglomerated nanoparticles. The complexes exhibited thermosensitive aggregation behavior near the lower critical solution temperature of the poly(N-isopropylacrylamide) component.     

Modelling the solubility in Bayer liquors: A critical review and new models

An accurate and tractable model of solubility is a pre-requisite for any careful study of precipitation. Reviewing the abundant literature on the sodium aluminate solutions and Bayer Liquor, the authors point out the need for a new model for the apparent solubility of aluminium in actual Bayer Liquors and propose such a model, based on the well established Wesolowski's expression for the infinite dilution solubility and extended Debye–Hückel expression including a large empirical b I term for the “activity coefficient effect”. They suggest a chemical interpretation for this feature.     

An Advanced GAP/AN/TAGN Propellant. Part I: Ballistic Properties

A solid rocket propellant based on glycidyl azide polymer (GAP) binder plasticized with nitrate esters and oxidized with a mixture of ammonium nitrate (AN) and triaminoguanidine nitrate (TAGN) was formulated and characterized. Non‐lead ballistic modifiers were also included in order to obtain a propellant with non‐acidic and non‐toxic exhaust. This propellant was found to exhibit a burning rate approximately twice that of standard GAP/AN propellants. The exponent of the propellant is high compared to commonly used composite propellants but is still in the useable range at pressures below 13.8 MPa. This propellant may present a good compromise for applications requiring intermediate burn rate and impulse combined with low‐smoke and non‐toxic exhaust.     

Positional distribution of Δ5-acids in triacylglycerols from conifer seeds as determined by partial chemical cleavage

The positional distribution of various Δ5-acids in the seed triacylglycerols from several conifer species has been established after partial chemical degradation with Grignard reagent. The species studied were representative of four conifer families and were specially selected for their particularly high Δ5-acid contents. These species were Taxus baccata (Taxaceae; 5,9-18:2 acid, 11.9%), Larix decidua (Pinaceae; 5,9,12-18:3 acid, 28.5%), Sciadopytis verticillata (Taxodiaceae; 5,11,14-20:3 acid, 16.7%), and Juniperus communis (Cupressaceae; 5,11,14,17-20:4 acid, 19.8%). Calculations from the fatty acid compositions of triacylglycerols and of the mixture of 1,2- and 2,3-diacylglycerols generated by the Grignard reagent indicated that, for the four species, there was a considerable enrichment of Δ5-acids (generally more than ten times) in the 1,3-positions as compared to the 2-position, where Δ5-acids represented always less than 2% of total fatty acids esterified to triacylglycerols. This distribution was practically independent from the species (four families studied), the chainlength (18 or 20 carbon atoms), and the number of ethylenic bonds (two to four) in the Δ5-acids. Similar distributions were established for triacylglycerols from the seeds of three pine species that are available on a ton-scale: Pinus pinea, P. koraiensis, and P. pinaster. These observations confirm and extend previous studies conducted with other conifer species by similar techniques or by ¹³C-nuclear magnetic resonance spectroscopy. Consequently, the almost exclusive location of Δ5-acids in the external positions of triacylglycerols is now well established and appears to be a general feature of conifer seed oils.     

Influence of moisture content on the specific methanogenic activity of dry mesophilic municipal solid waste digestate

The objective of this study was to evaluate the influence of moisture content on the specific methanogenic activity (SMA) of a fresh dry mesophilic digestate from a municipal solid waste digester plant. For this purpose, SMA tests were performed under mesophilic conditions in 500 mL glass bottles of volume used as batch reactors, during a period of 20–25 days. Cellulose, propionate and acetate were used as substrates (5 g_COD kg^?1 digestate) at four different moisture contents, ranging from 65 to 82%. The moisture content strongly influenced the specific methanogenic activity. The highest SMA values were observed at a moisture content of 82% (11.1, 7.8 and 6.0 mg_COD g_VS^?1 d^?1 for cellulose, propionate and acetate spikes, respectively). SMA and moisture content were found to be linearly linked. Dry digestion at low water content is thus detrimental to the biological activity, probably due to physical limitations. Copyright © 2011 Society of Chemical Industry     

Carbon dioxide absorption by monoethanolamine in hollow fiber membrane contactors: A parametric investigation

A mathematical and numerical investigations on the gas–liquid absorption of carbon dioxide in monoethanolamine solutions in a hollow fiber membrane contactor device is described. The reactive absorption mechanism was built based on momentum and mass transport conservation laws in all three compartments involved in the process, i.e., the gas phase, the membrane barrier, and the liquid phase. The liquid absorbing solution flows in the fiber bore in which the velocity is assumed to obey a fully developed laminar flow, and the gas mixture circulates counter‐currently to the liquid flow in the shell side where the velocity is characterized by the Navier‐Stokes momentum balance equations. The average outlet gas and liquid concentrations, the reactive absorption flux, and the gas removal efficiencies are parametrically simulated with operational parameters such as gas flow rate, fresh inlet amine concentrations, and fiber geometrical characteristics. The shell velocity was described by other flow hydrodynamics models besides Navier‐Stokes and their simulated results were favorably compared to experimental data. © 2011 American Institute of Chemical Engineers AIChE J, 2012     

Evaluation of <Emphasis Type="Italic">Rhizopus oryzae</Emphasis> Lipase for the Determination of Regiodistribution in Triacylglycerols with Medium Chain Fatty Acids

The nutritional profile and rheological behaviors of lipids is both due to fatty acid composition and regiodistribution on external and internal positions of triacylglycerol. Actual methods for regiodistribution analysis having some restrictions, there is still a need for investigating a safe, simple and environmentally friendly method for the sn-2 position analysis that could especially be used for the analysis of fats containing medium and short chain fatty acids. The objective of this study was to evaluate the 1,3-selectivity and typoselectivity of Rhizopus oryzae lipase in the presence of short/medium chain fatty acids in partial hydrolysis conditions used for regiodistribution analysis. Structured triacylglycerols containing eight-carbon-chain length fatty acids in the sn -2 position were chemically synthesized using DCC/DMAP coupling agent and purification steps by flash-chromatography. The final product showed very high purity and was used as the substrate for 1,3-selectivity evaluation. Typoselectivity was assessed by investigating partial hydrolysis of equimolar blends of homogeneous TAG. This study confirmed the 1,3-selectivity of Rhizopus oryzae lipase in the hydrolysis conditions used, and revealed that this lipase was less influenced by fatty acids chain length than pancreatic lipase. Considering this, Rhizopus oryzae lipase appeared to be a good candidate for regiodistribution analysis of fats containing medium and short chain fatty acids.     

Volatile lactones from streptomycetes arise via the antimycin biosynthetic pathway

The volatiles released by several streptomycetes were collected by using a closed-loop stripping apparatus (CLSA) and analysed by GC-MS. The obtained headspace extracts of various species contained blastmycinone, a known degradation product of the fungicidal antibiotic, antimycin A(3b), and several unknown derivatives. The suggested structures of these compounds, based on their mass spectra and GC retention indices, were confirmed by comparison to synthetic reference samples. Additional compounds found in the headspace extracts were butenolides formed from the blastmycinones by elimination of the carboxylic acid moiety. Analysis of a gene knockout mutant in the antimycin biosynthetic gene cluster demonstrated that all blastmycinones and butenolides are formed via the antimycin biosynthetic pathway. The structural variation of the blastmycinones identified here is much larger than within the known antimycins, thus suggesting that several antimycin derivatives remain to be discovered.     

Towards Heterogeneous and Green Versions of Os Dihydroxylation Catalysis

Os-catalyzed dihydroxylation will find more widespread application if truly heterogeneous catalysts are available which use O₂ or H₂O₂ as terminal oxidants. This paper discusses and critically evaluates the concepts by which Os can be anchored on solid supports. New methods are also available for reoxidation of hexavalent to octavalent Os.